9w23

DENV2 non-structural protein 1 (NS1) Stable Tetramer complexed with Heparin

spinqualitylabelsall models 9w23, resolution 3.12Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9w23 is a 4 chain structure with sequence from Dengue virus 2. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.12Å Ligands: GU6, Z9K, Z9L Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Dengue secreted non-structural protein 1 (sNS1) contributes to the vascular permeability symptom of severe dengue hemorrhagic fever. Previous flavivirus sNS1 structures suggest that they predominantly exist as loose tetramers. Here, we report two stable tetramer structures (3.1-3.6 A) together with loose tetramers. Formation of the stable tetramers involves a dramatic rearrangement of their N-terminal regions compared to the loose tetramers. We observe a higher molecular weight complex (HMWC) comprising dimeric sNS1 and heat shock proteins, which exhibits much lower endothelial hyperpermeability activity than the tetramer-enriched samples. We also determine high-resolution structures of the sNS1 complex with heparin, an analogue of the attachment factor heparan sulfate, showing that heparin binds to a conserved basic groove on the outer surface of the dimer, at the intra-dimer interface. Pre-incubation of sNS1 with heparin reduces its endothelial hyperpermeability activity. Our findings provide important structural information for future sNS1-based drug or vaccine design. Dynamic structures of dengue virus serotype 2 secreted NS1 and their interactions with heparan sulfate.,Zhou Q, Ng TS, Suthershinii G, Tan AWK, Kostyuchenko VA, Fibriansah G, Lok SM Nat Commun. 2026 Apr 15. doi: 10.1038/s41467-026-71970-3. PMID:41986350 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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